Fitting element with bio-compatible sealing

ABSTRACT

A fitting element is configured for coupling tubing to a fluidic device having a receiving cavity configured for receiving the fitting element, where the tubing has an inner contact surface of a biocompatible material, the inner contact surface being configured to contact a fluid to be conducted by the tubing, and the receiving cavity having a receiving contact surface of a bio-compatible material. The fitting element includes a first sealing element of a bio-compatible material configured for sealing to the bio-compatible material of the inner contact surface of the tubing, and a second sealing element configured for sealing against a pressure ambient to a pressure of the fluid in the tubing. Upon coupling of the tubing to the fluidic device, at least a portion of the receiving contact surface, the first sealing element, and the second sealing element enclose an interspace, each surface of the interspace being a bio-compatible material.

RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 13/811,655, which is a U.S. national phase application under 35 USC§ 371(c) of International Application Pub. No. WO/2012/010222 filed onDec. 13, 2010, naming S. Falk-Jordan as inventor. The entire disclosuresof U.S. patent application Ser. No. 13/811,655 and InternationalApplication Pub. No. WO/2012/010222 are hereby incorporated by referencein their entireties.

BACKGROUND

The present invention relates to a fitting element for a fluidic device,in particular in a high performance liquid chromatography application.

In high performance liquid chromatography (HPLC), a liquid has to beprovided usually at a very controlled flow rate (e.g. in the range ofmicroliters to milliliters per minute) and at high pressure (typically20-100 MPa, 200-1000 bar, and beyond up to currently 200 MPa, 2000 bar)at which compressibility of the liquid becomes noticeable. For liquidseparation in an HPLC system, a mobile phase comprising a sample fluidwith compounds to be separated is driven through a stationary phase(such as a chromatographic column), thus separating different compoundsof the sample fluid which may then be identified.

The mobile phase, for example a solvent, is pumped under high pressuretypically through a column of packing medium (also referred to aspacking material), and the sample (e.g. a chemical or biologicalmixture) to be analyzed is injected into the column. As the samplepasses through the column with the liquid, the different compounds, eachone having a different affinity for the packing medium, move through thecolumn at different speeds. Those compounds having greater affinity forthe packing medium move more slowly through the column than those havingless affinity, and this speed differential results in the compoundsbeing separated from one another as they pass through the column.

The mobile phase with the separated compounds exits the column andpasses through a detector, which identifies the molecules, for exampleby spectrophotometric absorbance measurements. A two-dimensional plot ofthe detector measurements against elution time or volume, known as achromatogram, may be made, and from the chromatogram the compounds maybe identified. For each compound, the chromatogram displays a separatecurve or “peak”. Effective separation of the compounds by the column isadvantageous because it provides for measurements yielding well definedpeaks having sharp maxima inflection points and narrow base widths,allowing excellent resolution and reliable identification of the mixtureconstituents. Broad peaks, caused by poor column performance, so called“Internal Band Broadening” or poor system performance, so called“External Band Broadening” are undesirable as they may allow minorcomponents of the mixture to be masked by major components and gounidentified.

An HPLC column typically comprises a stainless steel tube having a borecontaining a packing medium comprising, for example, silane derivatizedsilica spheres having a diameter between 0.5 to 50 μm, or 1-10 μm oreven 1-7 μm. The medium is packed under pressure in highly uniformlayers which ensure a uniform flow of the transport liquid and thesample through the column to promote effective separation of the sampleconstituents. The packing medium is contained within the bore by porousplugs, known as “frits”, positioned at opposite ends of the tube. Theporous frits allow the transport liquid and the chemical sample to passwhile retaining the packing medium within the bore. After being filled,the column may be coupled or connected to other elements (like a controlunit, a pump, containers including samples to be analyzed) by e.g. usingfitting elements. Such fitting elements may contain porous parts such asscreens or frit elements.

During operation, a flow of the mobile phase traverses the column filledwith the stationary phase, and due to the physical interaction betweenthe mobile phase and the stationary phase a separation of differentcompounds or components may be achieved. In case the mobile phasecontains the sample fluid, the separation characteristics are usuallyadapted in order to separate compounds of such sample fluid. The termcompound, as used herein, shall cover compounds which might comprise oneor more different components. The stationary phase is subject to amechanical force generated in particular by a hydraulic pump that pumpsthe mobile phase usually from an upstream connection of the column to adownstream connection of the column. As a result of flow, depending onthe physical properties of the stationary phase and the mobile phase, arelatively high pressure occurs across the column.

Fittings for coupling different components, such as separation columnsand conduits, of fluidic devices are commercially available and areoffered, for instance, by the company Swagelok (see for instancewww.swagelok.com). A typical tube fitting is disclosed in U.S. Pat. No.5,074,599 A.

U.S. Pat. No. 6,494,500 discloses a self-adjusting high pressure liquidconnector for use with high pressure liquid chromatography (HPLC)columns requiring liquid-tight and leak free seals between fittings andunions.

WO 2005/084337 discloses a coupling element comprising a male sealingelement. The male sealing element may have a generally cylindricalshape, and defines a fluid passageway therethrough for the transmissionof fluid. The male sealing element is secured to a ferrule which islocated within a cavity of the nut. The coupling element also has abiasing element disposed between a retaining ring and the ferrulelocated within the nut cavity. This biasing element facilitates afluid-tight, metal to metal (or metal to plastic, or plastic to plastic)seal between the male sealing element and female sealing element.

WO 2009/088663 A1 discloses liquid-chromatography conduit assemblieshaving high-pressure seals. A fluid-tight seal, proximal to the jointbetween two conduits, is provided, for example, through use of pressure,while a stabilizing seal, distal to the joint, is provided by adheringthe conduits to the tube.

A high pressure connect fitting is disclosed at US 2008/0237112 A1. Atip of a seal contacts the walls of a tapered sealing cavity to form aprimary seal. The volume of space between the very end of the tip andthe end of a sealing cavity defines a dead space. As the seal is axiallycompressed within an annular recess, the tip engages the walls of thetapered sealing cavity to form the primary seal, and further deforms tooccupy space otherwise associated with the dead space. As the tip of theseal engages the tapered sealing cavity, the end face of the sealcompresses against the end of the annular recess to form a secondaryseal extending radially around the tip of the seal.

U.S. Pat. No. 4,619,473 A describes a fluid passage connector for liquidchromatograph comprising a tube having a flat portion at one end and aseal seat surface. A similar device is known from the document “ViperCapillaries and Finger Tight Fitting System”, Dionex,www.dionex.com/en-us/webdocs/78632DS-Viper-Capillaries-17Jul2009-LPN2283.pdf.

WO 2010/000324 A1, by the same applicant, discloses a fitting forcoupling a tubing to another component of a fluidic device. The fittingcomprises a male piece having a front ferrule and a back ferrule bothbeing slidable on the tubing. The male piece has a first joint elementconfigured slidably on the tubing. A female piece has a recessconfigured for accommodating the front ferrule and the tubing, and asecond joint element configured to be joinable to the first jointelement. The back ferrule is configured in such a manner that, uponjoining the first joint element to the second joint element, the backferrule exerts a pressing force on the front ferrule to provide asealing between the front ferrule and the female piece, and the backferrule exerts a grip force between the male piece and the tubing.

International Patent Application PCT/EP2009/067646 discloses a fittingelement configured for providing a fluidic coupling to a fluidic device.An inlay is located in a cavity of a front side of a tubing. The inlayprotrudes over the front side, at least before coupling of the tubing tothe fluidic device. Upon coupling of the tubing to the fluidic device,the front side is fitted to the fluidic device for connecting a fluidpath of the tubing to a fluid path of the fluidic device, and the inlayprovides a sealing of the fluid path of the tubing and the fluidicdevice.

A bio-compatible column for use in liquid chromatography applications isknown from U.S. Pat. No. 5,651,885 A.

Fittings made of PEEK material are known e.g. from webstore.idexhs.com/Products/specsheet.asp?vSpecSheet=257&vPart=F-301&vFrom=L, whichhowever only allow limited pressure application below 300-400 bar.

Ni-coated PEEK-Capillaries are disclosed atwww.vici.com/tube/ni-cladpeek.php.

DISCLOSURE

It is an object of the invention to provide an improved fitting, inparticular for HPLC applications requiring biocompatibility.

According to the present invention, a fitting element is provided, whichis configured for coupling a tubing to a fluidic device. The fluidicdevice has a receiving cavity configured for receiving the fittingelement. The tubing has an inner contact surface comprised of abio-compatible material, wherein the inner contact surface is configuredto be in contact with a fluid to be conducted by the tubing. Thereceiving cavity has a receiving contact surface comprising abio-compatible material. The fitting element comprises a first sealingelement having a bio-compatible material and being configured forproviding a sealing to the bio-compatible material of the inner contactsurface of the tubing. The fitting element further comprises a secondsealing element configured for sealing against a pressure ambient to apressure of the fluid in the tubing. Upon coupling of the tubing to thefluidic device, at least a portion of the receiving contact surface, thefirst sealing element, and the second sealing element enclose aninterspace, wherein each surface of the interspace is comprised of abio-compatible material.

Embodiments of the invention allow providing a coupling between thetubing and the fluidic device which fulfills the requirements withrespect to bio-compatibility. The two-stage sealing provided by thefirst and second sealing elements allows sealing the coupling betweenthe tubing and the fluidic device even at higher pressure of the fluidto be conducted by the tubing. Embodiments may allow secure sealing atfluid pressure beyond 600 bar and even in the range of 1000-1500 bar andbeyond. By providing the interspace being enclosed by bio-compatiblesurfaces only, the fitting element ensures a bio-compatible coupling ofthe tubing to the fluidic device even at higher pressure.

The bio-compatible material can be mainly used to avoid e.g. releasingions from metal parts which may contaminate the sample and/or a columnpackaging material, and/or adversely affect the analysis itself.

The two-stage sealing provides a sealing in first stage where the tubingcouples to the fluidic device, and an additional sealing stage in orderto securely seal against a fluid pressure in the fluid path. In otherwords, the first sealing element may provide a low(er) pressure sealing(e.g. at the front side of the tubing), and the second sealing elementmay provide a high(er) pressure sealing located, for example, at oralong a lateral side of the tubing.

It is to be understood that in particular the front side at theconnection of the tubing to the fluidic device is often very difficultto seal, as in particular the shape of the counterpart element to thetubing might vary from one fluidic device to another and/or might havesurface imperfections. However, contact pressure in particular in axialdirection of the tubing might be limited in order to avoid or reducedestruction or deformation of the components involved. With increasingfluid pressure, for example in the range of thousand bar and beyond,conventional fitting systems have been often shown not to be sufficientand may lead to leaking and/or cross contamination. The two stagesealing, however, may allow that fluid even when “leaking” through thefirst stage of the first sealing element is fully sealed at the secondstage and is limited from returning back into the fluid path, forexample during normal application.

For example in an HPLC application, the front sealing provided by thefirst sealing element may allow fluid to pass (“leak”) duringpressurizing of the system (when the pressure in the system is raised tothe desired target pressure). While the second sealing element fullyseals so that no fluid can leak through such second sealing element, theinterspace between the first and second sealing elements may becomefilled with fluid. However, as such fluid applied in the pressurizingphase in HPLC is normally only solvent which does not contain anysample, the interspace will thus be filled only with such (non-samplecontaining) solvent, so that no sample contamination can occur even whenfluid contained in the inner space may return back into the fluid path.Further, it is to be understood that system pressure (after sample hasbeen introduced) in HPLC usually changes slowly and within a narrowrange compared to the system pressure, so that the fluid in theinterspace is kept within the interspace and “sees” only very low“driving force” to communicate with the fluidic path of the inside ofthe tubing. Such embodiments thus provide a “chromatographic sealing” bythe first sealing element (e.g. at the front side) and a “systempressure sealing” by means of the second sealing element. The term“chromatographic sealing” can be understood as a sealing sufficientduring a sample run in an HPLC system, so that carry over (i.e. thesample is temporarily trapped and released later), or external bandbroadening (e.g. sample is guided to a “dead space” where the sample isreleased only by diffusion) can be avoided or at least limited,preferably while maintaining pressure within a narrow range when samplehas been introduced in the HPLC-System.

In one embodiment, the first sealing element is configured for sealingthe tubing in a region of an end of the tubing where the tubing is to becoupled to the fluidic device. In other words, the first sealing elementprovides a front-sided sealing at a front side of the tubing where thetubing abuts the receiving contact surface of the receiving cavity. Uponcoupling of the tubing to fluidic device, the first sealing element mayprovide a first sealing stage at the front side of the tubing where thetubing is pressing to the receiving contact surface within the receivingcavity.

In embodiments, the first sealing element is comprised of thebio-compatible material. Each surface of the first sealing element maybe comprised of the bio compatible material. Alternatively or inaddition, each surface of the first sealing element, which may come incontact with the fluid to be conducted by the tubing, is comprised ofthe bio-compatible material.

In embodiments, the first sealing element is either removeably orfixedly coupled to the tubing. The first sealing element may be coupledto the tubing by at least one of: pressing, clipping, a direct moldingprocess, a welding process, a gluing process, a thermal process (such asthermo-forming), re-casting, re-melting, partial heating, laser heating,or ultra-sonic heating. It is clear that other ways or methods ofcoupling may be provided accordingly as long as fulfilling therequirements of either fixedly or removeably coupling the sealingelements to the tubing.

The first sealing element may at least partly cover a front side of thetubing, wherein the front side represents an axial end of the tubing. Insuch embodiments, the first sealing element may protrude in an axialdirection (with respect to the tubing) over the front side of thetubing, at least before coupling of the tubing to the fluidic device. Inalternative embodiments, upon coupling of the tubing to the fluidicdevice, the front side is fitted to the fluidic device for connecting afluid path of the tubing to a fluid path of the fluidic device, and thefirst sealing element provides a sealing of the fluid path of the tubingand the fluidic device. Alternatively or in addition, upon coupling ofthe tubing to the fluidic device, the front side presses to a contactside of the fluidic device for coupling the fluid path of the tubing tothe fluid path of the fluidic device. The first sealing element maylaterally extend over the front side of the tubing. In such embodiment,the front side may represent a stopper for a forward motion of thetubing when the tubing is coupled to the fluidic device.

In one embodiment, the first sealing element comprises an outer surfacewhich is facing the fluidic device upon coupling. The outer surfacecomprises a structure configured for increasing a surface pressurebetween the first sealing element and the fluidic device. The structuremay comprise at least one of: one or more indentations (preferablyconcentric indentations), protrusions (preferably concentricprotrusions), micro-cavities or inclusions for further acceptance ofsealing components or impregnation.

Embodiments of the fitting element according to the invention provide afront-sided sealing of the tubing at the transition to the fluidicdevice. The sealing properties can be adapted and adjusted to therespective application, in particular by the design parameters such asmaterial, size and shape of the fitting element or parts thereof (e.g.the inlay), and height e.g. of a protrusion over the front side of thetubing. By adequately selecting such design parameters, the fittingelement will be pressed against the front side when the tubing iscoupled to fluidic device, and will thus provide a sealing.

In case the first sealing element is provided of a material which can bedeformed under the influence of pressure when coupling the tubing to thefluidic device, such as a polymer material (e.g. PEEK), the tubing mayprovide a stopper functionality, so that the first sealing element isonly deformed until the front side is reached. In other words,deformation of the inlay will only occur until a protruding portion ofthe first sealing element has been deformed. This allows limiting theamount of deformation and allows ensuring that the fluid flow path isnot excessively narrowed under the influence of continuing pressure.

In one embodiment, the first sealing element is or comprises an inlaylocated in a cavity of a front side of the tubing. Such cavity might beembodied in accordance as disclosed in the aforementioned Internationalapplication PCT/EP2009/067646, which disclosure with respect to theinlay shall be incorporated herein by reference.

The inlay may protrude over the front side, at least before coupling ofthe tubing to the fluidic device. Upon coupling of the tubing to thefluidic device, the front side may be fitted to the fluidic device forconnecting a fluid path of the tubing to a fluid path of the fluidicdevice, so that the inlay provides a sealing of the fluid path of thetubing and the fluidic device. The cavity may be located in a centerposition of the front side of the tubing and opening into the flow pathof the tubing.

In preferred embodiments, the inlay is formed into the cavity, whichcavity is preferably situated in the center of the front side of thetubing. The inlay may be form-fitted and/or pressed-fitted into thecavity. The inlay may be fixed into the cavity by applying a directmolding process, a welding process, a gluing process and/or thermalprocess. Such thermal process may be any or a combination ofthermoforming, recasting, remelting, partial heating, laser heating, andultrasonic heating. The inlay may be preformed (outside the cavity) andthen inserted into the cavity. Alternatively, the inlay may also bedirectly formed into the cavity, e.g. by injection molding whereas thetubing has to be placed within the injection mold while injecting thepolymeric material.

The inlay is preferably fixedly coupled into the cavity, and may resultin an integral part to the tubing. This allows that the inlay staysfixed to tubing even when removing the tubing from the fluidic deviceafter it has been coupled thereto. This can overcome a common problem inconventional fittings, such as in the aforementioned U.S. Pat. No.4,619,473 type fittings, that a part of the fitting (in particular thefront-sided sealing) may stick/remain in a receiving cavity of thefluidic device after removal of the fitting element. In applicationse.g. where the inlay may (partly) remain in the receiving cavity afteropening the fitting, the inlay may also be loosely inserted into thecavity. Alternatively, the inlay may be provided of a material, whichallows that the inlay will be fixedly formed into the cavity underapplication of pressure when coupling the tubing to the fluidic device.

For fixedly coupling the inlay into the cavity, preferably a thermalprocess can be used, since a melting contact to the tubing may preventgaps or voids which may cause further artifacts in liquid guiding, e.g.external band broadening or carry over.

In one embodiment, the inlay extends laterally over the cavity and atleast partly onto the front side of the tubing. In other words, theinlay extends radially over the boundaries of the cavity, so that aportion of the inlay sits on at least a portion of the front side of thetubing. This combines the sealing properties of the inlay with asqueeze-type gasket but may also limit/reduce the stopper functionalityprovided by the tubing. In order to limit the sealing provided by thecavity to the front side only, the inlay may be laterally (or radially)limited to the front side only and thus not extend to the lateralside(s) of the tubing, e.g. in order to ensure that the tubing can beremoved from the fluidic device after coupling.

In one embodiment the inlay only fills the cavity within the tubing, andthe protrusion of the inlay deforms without lateral deformation into agap between tubing and fluidic device, when being compressed.

In one embodiment, the inlay comprises a flow path, so that when thetubing is coupled to the fluidic device, the flow path of the inlay is(smoothly) coupled between the flow paths of the tubing and the fluidicdevice. In other words, the inlay provides a portion of the fluid flowpath which guides the liquid and may thus reduce or eliminatedisturbances. In one embodiment, the cavity is located in a centerposition of the front side of the tubing and opens into the flow path ofthe tubing.

In one embodiment, the inlay comprises an outer surface which is facingthe fluidic device upon coupling. The outer surface may comprise astructure configured for increasing surface pressure between the inlayand the fluidic device when the tubing is coupled to the fluidic device.Such increasing of surface pressure may improve the sealing properties,for example by allowing withstanding of higher pressure. Further, suchstructure may also allow reducing the material (of the inlay) involvedwhen tightened. In other words, by adequately designing the structurethe material which has to be displaced under the influence of pressurefor providing the desired sealing characteristic can be reduced. Thestructure may comprise one or more indentations, preferably (radially)concentric indentations, one or more protrusions, preferably (radially)concentric protrusions, one or more micro-cavities or other kind ofinclusions for further acceptance of sealing components or impregnation,or any kind of combination thereof. Within these cavities or inclusions,a material different than that of the inlay can be fixed. Such materialmay be of lowered strength and/or increased formability and/or effect awetting behavior (e.g. a hydrophobicity of liquid wetted surfaces).

In one embodiment, the inlay is made of or comprises a polymer material,such as PEEK, PEKK, PE, polyimide, a metal material such as gold,titanium, and SST20 alloys (preferably with low yield strength), and/ora ceramic such as ZrO₂, Al₂O₃, or Steatit. The material is preferablyselected in order to adapt to an opposed surface of the fluidic devicewithout leakage under a certain pressure drop. The inlay may also have acoating, such as gold, a polymer e.g. as a fluoropolymer, allowingcovering and/or filling smaller surface roughness when being pressed. Incase of a metal type inlay, (i.e. the inlay is comprised of a metal), ametal coating is preferably selected, such as gold. In case of a polymertype inlay, (i.e. the inlay is comprised of a polymer), a polymercoating is preferably selected, such as a fluoropolymer.

When applying a tubing having inner and outer tubings, the inlay can beconfigured to cover a contact region at an axial end of the tubingresulting where the inner and outer tubings are abutting together. Suchcontact region occurring at the front side of the tubing may show a gapbetween the inner and outer tubings or any other kind of surfaceirregularity and usually requires an extra step of closing such gapand/or surface irregularity. Often, certain surface irregularities stillremain which may then lead to cross contamination, for example betweendifferent sample runs in HPLC. By designing the inlay to cover the axialend of the contact region, e.g. in that such contact region is withinthe cavity of the tubings, the inlay can close any surface irregularityand thus reduce or even avoid potential cross contamination.

In case the inner tubing is made of a bio-compatible material, such as apolymer (e.g. PEEK), and the outer tubing may be provided in particularfor increasing mechanical strength but may not be bio-compatible atleast as required, the inlay can be fixed to the inner tubing to becomefluid tight. The cavity may then also be provided of a bio-compatiblematerial, such as a polymer (e.g. PEEK), and seal the fluid againstcontacting the outer tubing, so that bio-compatibility of the tubing canbe ensured. Fixing of the cavity to the inner tubing can be preferablyachieved as aforedescribed, for example by a thermal process inparticular by laser or ultrasonic heating.

In one embodiment, the first sealing element comprises a front socketsurrounding the tubing in a region of an end of the tubing where thetubing is to be coupled to the fluidic device. The front socketcomprises a bio-compatible material and provides the sealing to thebio-compatible material of the inner contact surface of the tubing.

The front socket may also comprise the second sealing element, so thatthe front socket provides the first sealing stage provided by the firstsealing element as well as the second sealing stage provided by thesecond sealing element. Thus, the front socket may provide the first andsecond sealing elements in an integral component.

In one embodiment, the second sealing element provides—upon coupling ofthe tubing to the fluidic device—a second sealing stage for sealing thereceiving cavity along a side of the tubing within the receiving cavity.

The second sealing element may comprise a front ferrule. The frontferrule may be slidable on the tubing at least before coupling thetubing to the fluidic device. The front ferrule may have a conicallytapered front part configured to correspond to a conical portion of thereceiving cavity of the fluidic device. Upon coupling of the tubing tothe fluidic device, the conically tapered front part presses against theconical portion of the receiving cavity for sealing against the pressureof the fluid part of the tubing.

The second sealing element may be configured for sealing the receivingcavity of the fluidic device, when the receiving cavity receives thefitting element upon coupling of the tubing to the fluidic device. Thefirst sealing element may be sealing the receiving cavity at the frontside of the tubing, and the second sealing element may be sealing thereceiving cavity along a side of the tubing within the receiving cavity.

In one embodiment, the fitting element further comprises a back socketsurrounding the tubing in a region of an end of the tubing where thetubing is to be coupled to the fluidic device. The back socket isconfigured to provide mechanical support to the second sealing elementexerting a force towards the tubing. The back socket thus allowsproviding sufficient mechanical support, which may be required forsealing of the second sealing element in particular in high pressureapplications beyond 500 bar.

In one embodiment, the tubing comprises an inner tubing and an outertubing. The outer tubing surrounds the inner tubing and providesmechanical support to the inner tubing. The inner tubing is comprised ofa material different than the outer tubing. The inner tubing maycomprise the bio-compatible material in order to ensure a biocompatibletransport of the fluid. The outer tubing may comprise the first sealingelement and/or the back socket.

In one embodiment the inner tubing is a tube-in-tube arrangement whereinthe liquid leading tubing is made of fused silica or glass, and thesecond tubing covering the fused silica or glass tubing is made of metalor polymeric material.

In one embodiment, the second sealing element at least partly surroundsat least one of the front socket and the back socket.

In one embodiment, at least one bio-compatible material comprises atleast one material of: a polymer (preferably polyether ether ketone(PEEK), polyetherketoneketone (PEKK), polyethylene (PE),polytetrafluoroethylene (PTFE, e.g. TEFLON® material) and/or polyimide),a metal (preferably gold and/or titanium), and a ceramic.

The tubing may be made or comprise at least one of a group consisting ofa metal, stainless steel, titanium, a plastic, a polymer, glass, quartz,and ceramic. The tubing may have a lumen having a diameter of less than0.8 mm, particularly less than 0.2 mm. The tubing may have a circular,an elliptical or rectangular shape. The tubing may be or comprise acapillary.

In embodiments, the fitting element comprises a pre-load elementconfigured for pressing—upon coupling of the tubing to fluidicdevice—the tubing in an axial direction of the tubing against thefluidic device. The pre-load element may be configured for pressing—uponcoupling of the tubing to the fluidic device—a front side of the tubingin axial direction of the tubing against the fluidic device. Thepre-load element may exert at least one of a spring-loaded and springbiased pressing force on the front side of the tubing. The pre-loadelement may be configured to promote—upon joining of the tubing and thefluidic device—a forward motion of the tubing towards the fluidicdevice. The pre-load element may be configured to promote—upon joiningof the tubing and the fluidic device—a forward motion of the tubingtowards a stopper of the tubing.

In one embodiment, the fitting element comprises a gripping elementconfigured for promoting—upon coupling of the tubing to the fluidicdevice—a grip force to mechanically connect the gripping element withthe tubing. Alternatively or in addition, the fitting element maycomprise a first joint element configured for joining to the fluidicdevice, preferably by a screw connection.

In one embodiment, a fitting element is configured for coupling a tubingto a fluidic device. The tubing has an inner contact surface comprisedof a bio-compatible material, and the inner contact surface isconfigured to be in contact with a fluid to be conducted by the tubing.The fitting element comprises a front socket and a back socket. Thefront socket and the back socket each surround the tubing in a region ofan end of the tubing where the tubing is to be coupled to the fluidicdevice. The front socket comprises a bio-compatible material andprovides a bio-compatible sealing to the biocompatible material of theinner contact surface of the tubing. The back socket is configured toprovide mechanical support to an outer fitting member exerting a forcetowards the tubing.

In one embodiment, a fitting is configured for coupling a tubing to afluidic device. The tubing has an inner contact surface comprised of abio-compatible material, and the inner contact surface is configured tobe in contact with a fluid to be conducted by the tubing. The fittingcomprises a fitting element according to any of the aforementionedembodiments. The fluidic device comprises a receiving cavity configuredfor receiving the fitting element. The receiving cavity comprises areceiving contact surface comprising a bio-compatible material. Uponcoupling of the tubing to the fluidic device, the first sealing elementprovides a sealing to the bio-compatible material of the inner contactsurface of the tubing, the second sealing element seals against apressure ambient to a pressure of the fluid in the tubing, and a fluidpart of the tubing is connected to a fluid path of the fluidic device.

In one embodiment, the fitting element comprises a pre-load element, agripping element, and a first joint element. The receiving cavitycomprises a second joint element. Upon coupling of the tubing to thefluidic device, the pre-load element presses the tubing in an axialdirection of the tubing against the fluidic device, the gripping elementpromotes a grip force to mechanically connect the gripping element withthe tubing, and the first joint element joins to the second jointelement of the fluidic device.

The fluidic device may be or comprise at least one of: a second tubing,an apparatus, an HPLC device, a fluid separation device, a fluidhandling device, a measurement device, etc.

The fluidic device may comprise a processing element configured forinteracting with a sample fluid.

The fluidic device may be configured to conduct a sample fluid throughthe fluidic device, and/or to analyze at least one of a physical,chemical or biological parameter of at least one compound of a samplefluid. The fluidic device might be configured as a fluid separationsystem for separating compounds of a sample fluid and/or a fluidpurification system for purifying a sample fluid.

The terms “radial” and “axial”, as used herein, shall be defined withrespect to the tubing having an axial direction in the direction of thefluid flow and a radial direction perpendicular to the axial direction.The tubing extends in axial direction, and the flow path of the tubingis radially enclosed by the tubing.

The terms “fitting” and “fitting element”, as used herein, shall bothrelate to coupling a tubing to a fluidic device. The term “fitting”shall cover all components required for coupling the tubing to thefluidic device, and may even comprise the tubing and/or the fluidicdevice, or parts thereof. The term “fitting element” shall cover a partof the fitting.

An embodiment of the present invention comprises a fluid separationsystem configured for separating compounds of a sample fluid in a mobilephase. The fluid separation system comprises a mobile phase drive, suchas a pumping system, configured to drive the mobile phase through thefluid separation system. A separation unit, which can be achromatographic column, is provided for separating compounds of thesample fluid in the mobile phase. The fluid separation system furthercomprises a fitting element and/or fitting as disclosed in any of theaforementioned embodiments for coupling a tubing (provided forconducting the mobile phase) to a fluidic device in such fluidseparation system. The fluid separation system may further comprise asample injector configured to introduce the sample fluid into the mobilephase, a detector configured to detect separated compounds of the samplefluid, a collector configured to collect separated compounds of thesample fluid, a data processing unit configured to process data receivedfrom the fluid separation system, and/or a degassing apparatus fordegassing the mobile phase. The fluidic device to which the tubing is orcan be coupled can be any of such devices, and plural of such fittingsor fitting elements may be used within such fluid separation system.

Embodiments of the present invention might be embodied based on mostconventionally available HPLC systems, such as the Agilent 1200 InfinitySeries, or the Agilent 1100 HPLC series (all provided by the applicantAgilent Technologies—see www.agilent.com—which shall be incorporatedherein by reference).

The separating device preferably comprises a chromatographic columnproviding the stationary phase. The column might be a glass, plasticmaterial or steel tube (e.g. with a diameter from 50 μm to 5 mm and alength of 1 cm to 1 m) or a microfluidic column (as disclosed e.g. in EP1577012 or the Agilent 1200 Series HPLCChip/MS System provided by theapplicant Agilent Technologies, see e.g.www.chem.agilent.com/Scripts/PDS.asp?lPage=38308).

The mobile phase (or eluent) can be either a pure solvent or a mixtureof different solvents. It can be chosen e.g. to minimize the retentionof the compounds of interest and/or the amount of mobile phase to runthe chromatography. The mobile phase can also be chosen so that thedifferent compounds can be separated effectively. The mobile phase mightcomprise an organic solvent like e.g. methanol or acetonitrile, oftendiluted with water. For gradient operation water and organic aredelivered in separate bottles, from which the gradient pump delivers aprogrammed blend to the system. Other commonly used solvents may beisopropanol, tetrahydrofuran (THF), hexane, ethanol and/or anycombination thereof or any combination of these with aforementionedsolvents.

The sample fluid might comprise any type of process liquid, naturalsample like juice, body fluids like plasma or it may be the result of areaction like from a fermentation broth.

The fluid is preferably a liquid but may also be or comprise a gasand/or a supercritical fluid (as e.g. used in supercritical fluidchromatography—SFC—as disclosed e.g. in U.S. Pat. No. 4,982,597 A).

The pressure in the mobile phase might range from 2-200 MPa (20 to 2000bar), in particular 10-150 MPa (100 to 1500 bar), and more particularly50-120 MPa (500 to 1200 bar).

BRIEF DESCRIPTION OF DRAWINGS

Other objects and many of the attendant advantages of embodiments of thepresent invention will be readily appreciated and become betterunderstood by reference to the following more detailed description ofembodiments in connection with the accompanied drawing(s). Features thatare substantially or functionally equal or similar will be referred toby the same reference sign(s). The illustrations in the drawings areschematic.

FIG. 1 shows in schematic view a liquid separation system 10, inaccordance with embodiments of the present invention, e.g. used in highperformance liquid chromatography (HPLC).

FIG. 2 illustrates a cross-sectional view of a fitting 100 according toan exemplary embodiment.

FIG. 3 shows in more detail an exemplary embodiment of fittingcomponents 300 of the fitting 100.

FIG. 4A is a cross-sectional view of fitting components according toanother embodiment.

FIG. 4B is a cross-sectional view of fitting components according toanother embodiment.

FIG. 5 is a cross-sectional view of fitting components according toanother embodiment.

FIG. 6 is a cross-sectional view of fitting components according toanother embodiment.

FIG. 7A is a cross-sectional view of fitting components according toanother embodiment.

FIG. 7B is a cross-sectional view of fitting components according toanother embodiment.

FIG. 7C is a cross-sectional view of fitting components according toanother embodiment.

FIG. 8A is a cross-sectional view of fitting components according toanother embodiment.

FIG. 8B is a cross-sectional view of fitting components according toanother embodiment.

FIG. 8C is a cross-sectional view of fitting components according toanother embodiment.

Referring now in greater detail to the drawings, FIG. 1 depicts ageneral schematic of a liquid separation system 10. A pump 20 receives amobile phase from a solvent supply 25, typically via a degasser 27,which degases and thus reduces the amount of dissolved gases in themobile phase. The pump 20—as a mobile phase drive—drives the mobilephase through a separating device 30 (such as a chromatographic column)comprising a stationary phase. A sampling unit 40 can be providedbetween the pump 20 and the separating device 30 in order to subject oradd (often referred to as sample introduction) a sample fluid into themobile phase. The stationary phase of the separating device 30 isconfigured for separating compounds of the sample liquid. A detector 50is provided for detecting separated compounds of the sample fluid. Afractionating unit 60 can be provided for outputting separated compoundsof sample fluid.

While the mobile phase can be comprised of one solvent only, it may alsobe mixed from plural solvents. Such mixing might be a low pressuremixing and provided upstream of the pump 20, so that the pump 20 alreadyreceives and pumps the mixed solvents as the mobile phase.Alternatively, the pump 20 might be comprised of plural individualpumping units, with plural of the pumping units each receiving andpumping a different solvent or mixture, so that the mixing of the mobilephase (as received by the separating device 30) occurs at high pressureand downstream of the pump 20 (or as part thereof). The composition(mixture) of the mobile phase may be kept constant over time, the socalled isocratic mode, or varied over time, the so called gradient mode.

A data processing unit 70, which can be a conventional PC orworkstation, might be coupled (as indicated by the dotted arrows) to oneor more of the devices in the liquid separation system 10 in order toreceive information and/or control operation. For example, the dataprocessing unit 70 might control operation of the pump 20 (e.g. settingcontrol parameters) and receive therefrom information regarding theactual working conditions (such as output pressure, flow rate, etc. atan outlet of the pump 20). The data processing unit 70 might alsocontrol operation of the solvent supply 25 (e.g. setting the solvent/sor solvent mixture to be supplied) and/or the degasser 27 (e.g. settingcontrol parameters such as vacuum level) and might receive therefrominformation regarding the actual working conditions (such as solventcomposition supplied over time, flow rate, vacuum level, etc.). The dataprocessing unit 70 might further control operation of the sampling unit40 (e.g. controlling sample injection or synchronization of sampleinjection with operating conditions of the pump 20). The separatingdevice 30 might also be controlled by the data processing unit 70 (e.g.selecting a specific flow path or column, setting operation temperature,etc.), and send—in return—information (e.g. operating conditions) to thedata processing unit 70. Accordingly, the detector 50 might becontrolled by the data processing unit 70 (e.g. with respect to spectralor wavelength settings, setting time constants, start/stop dataacquisition), and send information (e.g. about the detected samplecompounds) to the data processing unit 70. The data processing unit 70might also control operation of the fractionating unit 60 (e.g. inconjunction with data received from the detector 50) and provide databack.

For transporting liquid within the liquid separation system 10,typically tubings (e.g. tubular capillaries) are used as conduits forconducting the liquid. Fittings are commonly used to couple pluraltubings with each other or for coupling a tubing to any device. Forexample, fittings can be used to connect respective tubings to an inletand an outlet of the chromatographic column 30 in a liquid-sealedfashion. Any of the components in the fluid path (solid line) in FIG. 1may be connected by tubings using fittings. While the fluid path afterthe column 30 is usually at low pressure, e.g. 50 bar or below, thefluid path from the pump 20 to the inlet of the column 30 is under highpressure, currently up to 1200 bar, thus posing high requirements tofluid tight connections.

FIG. 2 shows an embodiment of a high pressure fitting 100 for coupling atubing 102 (having a (not shown) inner fluid channel for conductingliquid, e.g. the mobile phase with or without a sample fluid) to anotherfluidic device 103, such as chromatographic column 30 of FIG. 1. In theschematic view of FIG. 2, only the portion of the device 103 which isrelevant for the coupling with the tubing 102 is depicted.

The fitting 100 comprises a male piece 104 having a front ferrule 106(e.g. made of a polymer material) and having a back ferrule 108 (e.g.made of a metallic material). The front ferrule 106 and the back ferrule108 are integrally formed and are slidable together over the tubing 102(which might have a metal outer tubing or socket as shown later ingreater detail). Moreover, the male piece 104 has a first joint element110 configured slidably on the tubing 102. Thus, for mounting thefitting 100 on the tubing 102, the integrally formed configuration ofthe front ferrule 106 and the back ferrule 108 is slid over the tubing102, and subsequently the first joint element 110 is slid on the tubing102. The front ferrule 106, the back ferrule 108 and the first jointelement 110 together constitute the male piece 104.

After having slid the male piece 104 over the tubing 102, a female piece112 having a receiving cavity 114 (e.g. a recess) may be slid over thetubing 102 from the right-hand side to the left-hand side of FIG. 2. Thefemale piece 112 has the receiving cavity 114 configured foraccommodating the front ferrule 106, the back ferrule 108, a part of thefirst joint element 110, and the tubing 102, and has a second jointelement 116 configured to be joinable to the first joint element 110.The first and the second joint elements 110, 116 may be fastened to oneanother by a screw connection, as will be explained below in moredetail.

A lumen 126 of the front ferrule 106 is dimensioned for accommodatingthe tubing 102 with clearance. A lumen 132 of the back ferrule 108 isdimensioned for accommodating the tubing 102 with clearance. The firstjoint element 110 also has a lumen 150 configured for accommodating thetubing 102 with clearance.

The back ferrule 108 is configured such that upon joining the firstjoint element 110 to the second joint element 116, the back ferrule 108exerts a pressing force on the front ferrule 106 to provide a sealingbetween the front ferrule 106 and the female piece 112. Simultaneously,such joining has the consequence that the back ferrule 108 exerts a gripforce between the male piece 104 and the tubing 102, and that the frontferrule 106 is sealed against the tubing 102 to prevent any fluidleakage. The pressing force has a direction which is longitudinal(parallel to an extension of the tubing 102), whereas the grip force hasa direction which is perpendicular to the extension of the tubing 102.As the grip force, the back ferrule 108 generates a positive lockingforce between the male piece 104 and the tubing 102. This prevents thetubing 102 from laterally sliding after having fixed the two jointelements 110, 116 to one another.

As can be taken from FIG. 2, the front ferrule 106 has a conicallytapered front part 118 shaped and dimensioned to correspond to a conicalportion 120 of the receiving cavity 114 of the female piece 112. Thus, aform closure between the conical portion 120 of the receiving cavity 114on the one hand and the conically tapered front part 118 of the frontferrule 106 may be achieved. Moreover, the front ferrule 106 has aconically tapered back part 122 (which may also be arranged verticallyor upright) shaped and dimensioned to correspond to a slanted annularfront spring 124 of the back ferrule 108. Although the shapes of the twocomponents 122, 124 are adjusted to match to one another, it isnevertheless possible that upon exertion of corresponding forces, theslanted annular front spring 124 is bent. The slanted annular frontspring 124 is adapted for being bent, upon joining the first jointelement 110 to the second joint element 116, into an upright position(see arrow 152) to promote a forward motion of the front ferrule 106towards a stopper portion 148, which is a receiving contact surface (orpart of a receiving contact surface) of the receiving cavity 114 of thefemale piece 112.

An annular back spring 128 is provided as part of the back ferrule 108which is adapted to promote, upon joining the first joint element 110 tothe second joint element 116, a forward motion of the tubing 102 towardsa stopper portion 148 of the receiving cavity 114 of the female piece112 providing a spring-loading force.

Between the annular back spring 128 and the slanted annular front spring124 (two disk springs), a sleeve element 130 (a flat spring) isarranged. The sleeve element 130 is conically tapered and has a thickerportion facing the first joint element 110 and has a thinner portionfacing the front ferrule 106. A thickness s1 of the thinner portion issmaller than a thickness s2 of the thicker portion. These differentthickness values allow the sleeve element 130 to improve the forcedistribution in a longitudinal direction of FIG. 2.

The first joint element 110 is configured for being joined to the secondjoint element 116 by a screw connection. Thus, in a portion 140, aninternal thread of the female piece 112 can be screwed into an externalthread in the first joint element 110 of the male piece 104. A usersimply has to fasten this screwing connection, and thereby automaticallyseals the front ferrule 106 against the female element 112 and exerts agrip between the back ferrule 108 and the tubing 102.

A slanted surface 134 of the first joint element 110 is configured forexerting a bending moment onto the annular back spring 128 of the backferrule 108. The slanted surface 134 includes an acute angle α=60° withan outer surface of the tubing 102. With such an acute angle 0<α<90°, adesired bending of the annular back spring 128 and the sleeve element130 of the back ferrule 108 and of an optional additional spring 136 maybe effected. As an alternative to the described configuration, it ispossible that the annular back spring 128 is slanted and the annularfront spring 124 is upright, or that both the annular back spring 128and the annular front spring 124 are slanted in a way that both of theminclude an acute angle with the sleeve element 130.

A force transmitting annular metal ring 136 (which supports additionalforce to the front ferrule 106 without increasing radial grip on tubing102) is arranged slidable on the tubing 102 between the back ferrule 108and the first joint element 110, and transmits a force exerted by thefirst joint element 110 to the back ferrule 108. The force transmissionelement 136 operates as a washer disk and is provided as a separateelement which is not integrally formed with a front ferrule 106 and aback ferrule 108. The additional metal ring 136 may be added to increasethe sealing force and the elastic deformation independent of thesupplied gripping force.

FIG. 2 shows a non-biased state of the fitting 100. In a sealedconfiguration, a first seal connection is achieved in a sealing region142 between the front ferrule 106 and the female part 112, and a secondsealing connection is achieved in a sealing region 144 between the frontferrule 106 and the tubing 102. In a front side (or frontal area) 146 ofthe tubing 102, is optionally possible to provide a polymeric coating inorder to further suppress sample contamination, since this measure mayfurther increase the sealing performance between the front side 146 andthe stopper portion 148.

In the following, the force transmission will be explained: After havingslid the front ferrule 106 and the back ferrule 108 on the tubing 102and after having slid the first joint element 110 onto the tubing 102,the first joint element 110 may be connected by screwing with the secondjoint element 116. This converts the back ferrule 108 into a biasedstate so that grip is generated between the tubing 102 and the backferrule 108. As the grip force increases the force longitudinal to thecapillary axis increases analog and supplies pressure to the sealingregions 142, 144. A corresponding force transmission further results inan upward pivoting of the annular front spring 124 of the back ferrule108, as indicated by arrow 152. This presses the polymer material of thefront ferrule 106 to a frontward position, i.e. towards the right-handside of FIG. 2 and supplies pressure to the sealing regions 142, 144.

FIG. 3 shows in more detail an exemplary embodiment of fittingcomponents 300 of the fitting 100, which are coupled with the tubing102. In other words, the device 103 (as depicted in FIG. 2) is omittedin FIG. 3 for the sake of clearer representation.

In the embodiment of FIG. 3, the tubing 102 has an inner tubing 310 andouter tubing 320. The outer tubing 320 surrounds the inner tubing 310and provides mechanical support to the inner tubing 310. The innertubing 310 is typically comprised of a material different from the outertubing 320. In this embodiment, the inner tubing 310 comprises abio-compatible material, such as PEEK. The inner tubing 310 includes aninner contact surface (as indicated by the lead line for referencenumeral 310) configured to contact a fluid to be conducted by the innertubing 310, i.e., the surface facing the interior of the inner tubing310. The inner contact surface may thus also comprise the bio-compatiblematerial. In order to provide sufficient mechanical support for theinner tubing 310, the outer tubing 320 in this embodiment shall comprisea nickel material, such as the aforementioned Ni-coated PEEK capillariesas referred to in the introductory part of the description.

The tubing-sided fitting components 300 of the embodiment of FIG. 3further comprise a first sealing element 330 (also acting as a frontsocket), a second sealing element 340, a back socket 350, the annularfront spring 124, and the first joint element 110. The first sealingelement 330 here is embodied as a front socket.

Further in FIG. 3 a portion of the receiving cavity 114, to which thetubing sided fitting elements 300 are abutting to, is also schematicallyillustrated.

The first sealing element 330 also comprises a bio-compatible material,for example PEEK, and closely seals to the inner tubing 310, thusproviding a biocompatible material transition between the bio-compatiblematerial of the inner tubing 310 and the bio-compatible material of thefirst sealing element 330. This can be achieved, for example, by havingthe polymers overlapping in the transitional area.

A front side 360 of the first sealing element 330 is abutting to thestopper portion 148 of the receiving cavity 114. This provides afront-sided sealing for the tubing 102 for sealing a fluid path 170 ofthe tubing 102 to a fluid path 175 of the fluidic device 103.

The second sealing element 340 is provided and embodied here by a frontferrule, which may be slidably attached to the tubing 102. The secondsealing element 340 abuts to the conically tapered front part 118 of thereceiving cavity 114 and thus provides a second sealing stage forsealing against a pressure ambience to a pressure of the fluid in thefluid paths 170, 175.

The illustration in FIG. 3 shows a state where the tubing 102 is coupledto the fluidic device 103 for sealingly coupling the tubing 102 with thefluidic device 103. The schematic representation in FIG. 3 shows that aninterspace 380 results where the front side 360 abuts to the stopperportion 148 and the second sealing element 340 abuts to the taperedfront part 118. It is clear that the representation of the interspace380 in FIG. 3 is only schematic and that the actual size of theinterspace 380 is typically much smaller and mainly depends ontolerances of the tubing 102 and the receiving cavity 103.

In operation, when the tubing 102 is conducting a fluid (e.g. a liquid)under high pressure, for example 500 bar and beyond, a portion of suchfluid might leak through the front side 360 into the interspace 380. Thetwo sealing stages provided by the front side 360 and the second sealingelement 340 are preferably configured that under normal conditions, i.e.when the tubing 102 is securely coupled to the receiving cavity 103, thesecond sealing stage of the second sealing element 340 fully sealsagainst the ambient of the interspace 380, so that any liquid will notleak from the interspace 380 to such ambient. However, more importantly,it is to be understood that under the influence of pressure variation,liquid from within the interspace 380 might leak back into the fluidpath 170, 175, for example when the pressure in the fluid path 170, 175falls below pressure in the interspace 380. In order to ensurebio-compatibility of the coupling, the interspace 380 has to beconfigured so as not to provide any surface which might interfere withthe requirement of bio-compatibility. For that purpose, each surface ofthe interspace 380 comprises a bio-compatible material. In theembodiment of FIG. 3, this means that at least the stopper portion (orreceiving contact surface) 148, the tapered front part 118 and an area385 in between the stopper portion 148 and the front part 118, thesurface of the second sealing element 340 facing the front part 118, andthe surface of the first sealing element 330 facing into the interspace380, and the front side 360 have to be provided with a surface of abio-compatible material. Accordingly, any fluid from within theinterspace 380, which might leak back into the flow path 170, 175 willnot adversely affect the required bio-compatibility. At the same time,the two-stage sealing provided by the first and second sealing elements330 and 340 allows designing the fitting 100 to be suitable even forhigh pressure applications beyond 500 bar and even up to 1000 bar andbeyond.

FIGS. 4-8 illustrate various embodiments in schematic cross-sectionalpart view. For the sake of simplicity, the given embodiments only showsuch components and views relevant for such embodiment, and the Figuresalso only depict partial views illustrating only one side of thethree-dimensional embodiments. It is clear that the embodiments aretypically rotationally and/or axially symmetric.

In the embodiment of FIGS. 4A and 4B, the tubing 102 is a PEEKcapillary. The first sealing element 330 and the second sealing element340 are provided in one component as a front ferrule 400, which shallalso be made of PEEK. The front ferrule 400 can also extend over thetubing 102 and seal the front side of the tubing as will be shown inFIG. 5.

To provide sufficient mechanical stability, the embodiments of FIGS. 4Aand 4B further comprise the back socket 350, which is preferably made ofa metal material such as stainless steel (SST), titanium, ceramic orother mechanically resistant materials. The back socket 350 and frontsocket 400 are designed so that at least a portion of the back socket350 is situated between the conically shaped second sealing element 340and the capillary 102, (at least) when assembled in the receiving cavity114 (not shown in FIG. 4), so that the back socket 350 can take up aradial force resulting from the second sealing element 340 being pressedagainst the conically shaped side 118 of the receiving cavity 103 (asdepicted in FIG. 3). The back socket 350 may provide a clearing recess420, into which material of the second sealing element 340 may flowunder the influence of the radial force, thus providing a form-fitbetween the front socket 400 and the back socket 350. Such form-fittingmay occur at the first assembly and fastening of the fitting 100 (seeFIG. 2) in order to ensure safe removing of all parts when disassemblingthe tubing 102 from the fitting 100. The back socket 350 may be weldedto the capillary 102 and thus be provided fixed with respect to thecapillary 102, while the front socket 400 may be provided slidable onthe tubing 102 and then be fixed to the back socket 350 by means of therecess clearance 420.

In the embodiment of FIG. 5, the capillary 102 shall also be made of abio-compatible plastic material, such as PEEK, and the back socket 350is made of a material providing sufficient mechanical support, such as ametal material. In the example of FIG. 5, the back socket 350 extends upto and over the front side 146 of the tubing 102. The back socket 350 ispreferably fixedly coupled with the tubing 102, for example, by a gluingor welding process. The first sealing element 330 is provided as a frontsocket and may be slid over the back socket 350 and then fixedly coupledto the back socket 350, for example, by a gluing or welding process. Thefirst sealing element 330 extends beyond and over the back socket 350 atthe front side 146. Sealing of non-biocompatible material can be ensurede.g. by pressing of the tubing 102 together with the back socket 350against the first sealing element 330, acting as a front socket. Thesecond sealing element 340, indicated in FIG. 5 by a dotted line, mayhere be an individual component or an integral part of the first sealingelement 330, for example in accordance with the embodiment shown inFIGS. 4A und 4B.

In the embodiment of FIG. 6, the tubing 102 comprises the inner tubing310 and the outer tubing 320 in accordance with the embodiment of FIG.3. The inner tubing 310 may be made of PEEK with the outer tubing 320being a metal material such as nickel. The first sealing element 330 isembodied as a front socket and extends over the lateral side of thetubing 102 up to and at least partly over the front side 146 of thetubing 102. The first sealing element 330 extends at the front side 146at least up to the inner tubing 310 and seals thereto.

In the embodiment of FIG. 6, the first sealing element 330 may furthercomprise an inlay 600, which can be embodied e.g. as disclosed in theaforementioned International application PCT/EP2009/067646. The inlay600 may be made of a material such as e.g. PEEK, PTFE.

Alternatively to the inlay 600, a cutting ring (not shown) can be used,which cuts into the inner tubing 310 e.g. upon mounting of the firstsealing element 330 and the tubing 102.

In the embodiment of FIGS. 7A-7C, the capillary 102 will also comprisethe inner tubing 310 and the outer tubing 320, with the inner tubing 310being made of a bio-compatible material, such as PEEK, and the outertubing 320 providing mechanical support and being made, for example, ofmetal such as nickel or stainless steel. The back socket 350 is madehere of a metal material and fixedly coupled to the outer tubing 320,for example, by a welding process as indicated by a weld seam 700.

In FIG. 7B, the first sealing element 330 is provided (again) in form ofa front socket and shall be made of a bio-compatible polymer material,such as PEEK. The first sealing element 330 is slid over the front-sidedend of the tubing 102 and at least partly extending over the front side146 of the tubing 102, at least until reaching the inner tubing 310.Alternatively, a cutting ring (not shown) can be used, which cuts intothe inner tubing 310, e.g. upon mounting of the first sealing element330 and the tubing 102, thus sealing against the outer tubing 320.

Similar to the embodiment shown in FIG. 4A, the back socket 350 in FIGS.7A-7C also comprises a recess clearance 420. When applying a force (asindicated in FIG. 7B by arrow F) onto the first sealing element 330, thefirst sealing element 330 can be deformed for at least partly fillingthe recess clearance 420, as indicated in FIG. 7C, in order to provide aform fit between the first sealing element 330 (front socket) and theback socket 350.

The embodiment of FIGS. 8A-8C substantially corresponds to theembodiment of FIGS. 7A-7C, with the tubing 102 also comprising abio-compatible inner tubing 310 and a support providing outer tubing320. The back socket 350, made of a metal material, shall also befixedly coupled to the outer tubing 320, for example, by a weldingprocess (indicated by weld seam 700).

Similar to FIG. 7B, the first sealing element 330 is slid in axialdirection (as indicated by the arrow) over the tubing 102 and partlyover the back socket 350. The first sealing element 330 comprises afirst locking feature 800, which in combination with a second lockingfeature 810 of the back socket 350 provides a locking, such as a snapfit of the first sealing element 330 to the back socket 350, when thefirst sealing element 330 is slid in place (as depicted in FIG. 8C).

In the position of FIG. 8C, the first sealing element 330 extends overthe front side 146 of the tubing 102 and seals to the inner tubing 310.

Further in FIG. 8C, the second sealing element 340 can be designed to atleast partly reach over the first and second locking element 800 and 810in order to provide a pressing force in radial direction to securelycouple the first sealing element 330 with the back socket 350 forexample by a form fitting.

In the embodiments of FIGS. 5-8, the conically shaped second sealingelement 340 may be provided as an individual component, such as a frontferrule, as indicated by the dotted line, or may be integrally embodiedwith either the first sealing element 330 or the back socket 350.

The invention claimed is:
 1. A tube and fitting system for use in aliquid chromatography system, comprising: a tube configured to beinserted into a receiving cavity of a fluidic device, the tube having apassageway therethrough opening at a front side of the tube, the tubecomprising: i) an outer tubing; and ii) a biocompatible inner tubinghaving the passageway therethrough and being located within the outertubing and extending to the front side, a first sealing elementcomprising a polymer and surrounding the tube including at the frontside, wherein the first sealing element provides a sealing to the innertubing and is configured to seal the receiving cavity at the front side;and a fitting configured to couple the tube to the fluidic device, thefitting comprising a back ferrule and a front ferrule, the front ferrulecomprising a tapered portion, wherein: the back ferrule comprises ametal, and the front ferrule comprises a polymer; and the back ferruleis configured to hold the tube by the outer tubing, and the frontferrule is configured to seal the receiving cavity along a lateral sideof the tube.
 2. The tube and fitting system of claim 1, wherein: thetapered portion is configured to, upon coupling the tube to the fluidicdevice, contact the fluidic device to form a sealing region between thetapered portion and the fluidic device, with the front ferrule beingpositioned between the sealing region and the back ferrule.